Chiral Sc catalyst

Enantioselective Diels-Alder reactions proceed smoothly in the presence of a chiral Sc catalyst, prepared in situ from Sc(OTf)3, R)- I )-l,l -bi-2-napluhol [(R)-BINOL], and a tertiary amine in dichloromethane.58 The catalyst is also effective in Diels-Alder reactions of an acrylic acid derivative with dienes (Scheme 14). 

Kobayashi reported an asymmetric Diels-Alder reaction catalyzed by a chiral lanthanide(III) complex 24, prepared from ytterbium or scandium triflate [ Yb(OTf)3 or Sc(OTf)3], (Zf)-BINOL and tertiary amine (ex. 1,2,6-trimethylpiperidine) [30], A highly enantioselective and endose-lective Diels-Alder reaction of 3-(2-butenoyl)-l,3-oxazolidin-2-one (23) with cyclopentadiene (Scheme 9.13) takes place in the presence of 24. When chiral Sc catalyst 24a was used, asymmetric amplification was observed with regard to the enantiopurity of (/ )-BINOL and that of the endoadduct [31 ]. On the other hand, in the case of chiral Yb catalyst 24b, NLE was affected by additives, that is, when 3-acetyl-l,3-oxazolidin-2-one was added, almost no deviation was observed from linearity, whereas a negative NLE was observed with the addition of 3-pheny-lacetylacetone. 

It was found that 3-acetyl-l, 3-oxazolin-2-one or 3-benzoyI-l,3-oxazolin-2-one was a good additive for stabilization of the chiral Sc catalyst, but that enantioselectivity could not be reversed by use of additives, behaviour different from that of the chiral Yb catalyst. This can be explained by the coordination number of Sc(III) and Yb(III)—whereas Sc(III) has up to seven ligands, specific coordination numbers of Yb(III) enable up to twelve [39],... 

Although Sc(OTf)3 has slightly different properties compared with other lanthanide triflates,the chiral Sc catalyst could be prepared from Sc(OTf)3, (R)-(+)-binaphthol, and a tertiary amine in dichloromethane [76]. The catalyst was also found to be effective in the Diels-Alder reactions of acyl-1,3-oxazolidin-2-ones with dienes. The amines employed in the preparation of the catalyst influenced the enantioselectivities strongly. For example, in the Diels-Alder reaction of 3-(2-butenoyl)-l,3-oxazolidin-2-one with cyclopentadiene (CH2C12, 0°C), the enantiomeric excesses of the endo adduct depended crucially on the amines employed aniline, 14% ee lutidine, 46% ee triethylamine, 51% ee 2,2,6,6-tetram-ethylpiperidine, 51% ee diisopropylethylamine, 69% ee 2,6-dimethylpiperid-ine, 69% ee 1,2,2,6,6-pentamethylpiperidine, 72% ee and cis-1,2,6-trimethyl-piperidine, 84% ee. 

It was also suggested that aggregation of the catalysts influenced the selectiv-ities in the Diels-Alder reactions, and the reaction of 3-(2-butenoyl)-l,3-oxazo-lidin-2-one with cyclopentadiene using ( R)-(+)-binaphthol in lower enantiomeric excesses was examined [84]. The results are shown in Fig. 1. Very interestingly, a positive nonlinear effect was observed in the chiral Sc catalyst. In the chiral Yb catalysts, on the other hand, the effect was dependent on the additives. The extent of asymmetric induction in catalyst A did not deviate from the enantiomeric excesses of ( R)-(+)-binaphthol in the range 60-100% ee [85], while a negative nonlinear effect was observed in catalyst B. These results can be ascribed to a difference in aggregation between the Sc catalyst, Yb catalyst A, and Yb catalyst B. 

Several examples of the chiral Sc(III)-catalyzed Diels-Alder reactions are shown in table 32. The highest enantioselectivities were observed when cis-1,2,6-tnmethylpiperidine was employed as an amine. 3-(2-butenoyl)-, 3-cinnamoyl-, and 3-(2-hexenoyl)-l,3-oxazolidin-2-ones reacted with cyclopentadiene smoothly in the presence of the chiral Sc catalyst to afford the corresponding Diels-Alder adducts in high yields and high selectivities. It should be noted that even 3 mol% of the catalyst was enough to complete the reaction, and the endo adduct was obtained in 92% ee. 

Asymmetric Catalysts Using Sc(OTf)3. The chiral Sc catalyst prepared from Sc(OTf)3, (i )-BINOL, and a tertiary amine in dichloromethane (eq 22) serves as an asymmetric catalyst for the Diels-Alder reactions of an acrylic acid derivative with dienes (eq 23). The highest enantioselectivities are observed when di -l,2,6-trimethylpiperidine is employed as the amine. Even 3 mol % of the catalyst is enough to complete the reaction yielding the endo adduct in 92% ee. The structure of the chiral Sc catalyst is indicated by C-NMR and IR spectra. A similar Sc(OTf)3/(R)-BINOL/diisopropylethylamine complex serves as an effective catayst for the Diels-Alder reaction of A-benzyloxy-carbonyl-l-aminobutadiene with 3-acyl-l,3-oxazolidin-2-one. ... 

In 1997 the application of two different chiral ytterbium catalysts, 55 and 56 for the 1,3-dipolar cycloaddition reaction was reported almost simultaneously by two independent research groups [82, 83], In both works it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 1 and alkenoyloxazolidinones 19 with endo selectivity. In the first study 20 mol% of the Yb(OTf)2-pyridine-bisoxazoline complex 55 was applied as the catalyst for reactions of a number of derivatives of 1 and 19. The reactions led to endo-selective 1,3-dipolar cycloadditions giving products with enantioselectivities of up to 73% ee (Scheme 6.38) [82]. In the other report Kobayashi et al. described a... 

With Binaphthol/M(OTf)3 Complexes (M = Yb, Sc) A chiral ytterbium triflate, derived from Yb(OTf)3, (R)-binaphthol, and a tertiary amine, has been applied to the enantioselective Diels-Alder reaction of cyclopentadiene with crotonoy 1 oxazolidinones. Among various tertiary amines, c/s-1,2,6-trimethyl piperidine was found to be highly effective [44] (Eq. 8 A.23). The unique structure of such chiral Yb catalysts is characterized by hydrogen bonding between the phenolic hydrogens of (R)-binaphthol and the nitrogens of tertiary amines. 

The metal-catalyzed allylboration is efficient to control both diastereoselectivity and enantioselectivity. The Sc(OTf)3-catalyzed reaction of chiral allyl boronates resulted in 90-98% ee for representative aldehydes (Equation (158)).624 628 629 The first catalytic enantioselective allylboration and crotylboration was achieved by a chiral lanthanide catalyst (Equation (159)).630... 

Although asymmetric versions of aza Diels-Alder reactions using chiral auxiliaries have been reported, only one example uses a stoichiometric amount of a chiral Lewis acid [44]. The first reported example of a catalytic enantioselective aza Diels-Alder reaction employed a chiral lanthanide catalyst [45]. A chiral ytterbium or scandium catalyst, prepared from Yb(OTf)3 or Sc(OTf)3, (i )-BINOL, and DBU, is effective in the enantioselective aza Diels-Alder reactions. The reaction of A-alkylidene- or N-arylidene-2-hydroxyaniline with cyclopentadiene proceeded in the presence of the chiral catalyst and 2,6-di-rerf-butyl-4-methylpyridine (DTBMP) to afford the corresponding 8-hydroxyquinoline derivatives in good to high yields with good to excellent diastereo- and enantioselectivity (Eq. 15). 

Catalytic asymmetric 1,3-dipolar cycloaddition of a nitrone with a dipolarophile has been performed using a chiral scandium catalyst [31]. The chiral catalyst, which was effective in asymmetric Diels-Alder reactions, was readily prepared from Sc(OTf)3, (7 )-(-i-)-BINOL, and d5 -l,2,6-trimethylpiperidine. The reaction of benzylbenzylide-neamine A-oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one was performed in the presence of the chiral catalyst to yield the desired isoxazolidine in 69 % ee with perfect diastereoselectivity (endolexo = > 99 1) (Sch. 8) [31,46], It was found that reverse enantioselectivity was observed when a chiral Yb catalyst, prepared from Yb(OTf)3, the same (i )-(-i-)-BINOL, and cd-l,2,6-trimethylpiperidine, was used instead of the Sc catalyst under the same reaction conditions. 

In the presence of the chiral scandium catalyst, the 1,3-dipolar cycloaddition of benzylbenzylideneamine A -oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one proceeds to yield the endo adduct endolexo 99/1) in 69% ee (eq 25). Chiral scandium complexes prepared from Sc(OTf)3 and 2,2 -bis(oxazolyl)-BESfOL derivatives also serve as efficient catalysts. ... 

Similarly, the catalyst prepared from jdterbium triflate (Yb(OTf)3) and Bl-NOL acts as efficient enantioselective catalyst in the reaction of the previous oxazolidine derivative and cyclopentadiene. The role of the amine addition is determined (113). The analogous chiral scandium catalysts are prepared from Sc(OTf)3, BINOL, and tertiary amine in the same manner (114). As a major difference between Yb(lll) and Sc(lll) chiral catalysts, their coordination numbers are thought although Sc(III) is known to coordinate up to seven ligands, the specific coordination of Yb(III) allows up to 12 ligands (115). 

A chiral Sc-pybox catalyst from Sc(OTf)3 catalyzes a highly enantioselective Michael-type indole Friedel-Crafts reactions with a variety of )3-substitnfed a, -unsaturated acyl phosphonates and -substituted a,j8-unsaturated 2-acyl imidazoles (Scheme 2). The acyl phosphonate products were efficiently ttansformed into the corresponding esters and amides, whereas the acyl imidazole prodncts were converted to more diverse functionalities snch as esters, amides, carboxyhc acids, ketones, and aldehydes. A nuld and efficient cleavage protocol for the diversification of the 2-acyl imidazole prodncts ntihzing methylating conditions was also developed. 

A chiral Sc-pybox catalyst catalyzes Lewis acid-catalyzed enantioselective alkenylation of air- and moisture-stable trimethylvinylsilanes under nuld conditions. Most products are highly crystalline sohds, which are ideally suited for industrial process chemistry (Scheme 4). 

Highly enantioselective Michael reactions of indanone and tetralone -ketoesters derivatives with a,P-unsaturated ketones promoted by a chiral scandium catalyst have been developed [123]. In the presence of Sc(OTf)3 and bipyridine (3), the reactions proceeded smoothly in dichloroethane at 40 °C to give the corresponding adducts in moderate to excellent yields with excellent enantioselectivities in most cases (Scheme 12.47). It was found that a lower concentration of the reaction mixture was key to attaining high selectivity. 

More recently, several approaches to catalytic, enantioselective Nazarov cyclizations have been developed [28]. Trauner reported that substrate 266 underwent electrocyclic rearrangement, furnishing 268 in 94 % ee in the presence of the chiral Sc-PYBOX catalyst 267 (Equation 30) [134]. The enantio-discriminating step in this cyclization is believed to be protonation of the intermediate enolate that ensues from the Nazarov cyclization. Rueping has documented enantioselective cyclizations of related dienones in the presence of the chiral phosphoric acid derivative 270 (Equation 31) [135]. Chiral Bronsted acid catalysis thus effected the cyclization of 269 to give products 271 (87% ee) and 272 (95% ee). 

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